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Insulin and its secretagogues are essential for some patients with type 2 diabetes (T2D) to maintain good glycemic control (GC), but severe hypoglycemia (SH) is a concern. This network meta-analysis aimed to find optimal glucose-lowering drug treatment regimens in terms of GC and SH in T2D patients. MEDLINE and EMBASE were used to identify trials that compared two or more treatments including insulins and/or sulfonylurea or glinides and that examined both GC and SH. Treatment hierarchy was expressed as the surface under the cumulative ranking curve (SUCRA) probabilities. We identified 137 eligible trials comprising 42 treatments. The use of insulins and non-insulin glucose-lowering agents except for sulfonylurea or glinide had a higher SUCRA than insulins only for hemoglobin A1c (A1C) (p = 0.01) changes and achievement of A1C

Mobility affects the ability of patients to live independently post-discharge. This study aimed to identify factors affecting the achievement of independent walking in patients after living donor liver transplantation (LDLT).This retrospective cohort study involved 40 patients who had undergone LDLT for severe hepatic dysfunction (Child-Pugh class C) in the Department of Transplant Surgery of our hospital between January 2010 and October 2019 and received physiotherapy during hospital admission. To identify factors associated with independent walking, we classified patients based on their ability to walk independently. We performed multiple logistic regression analyses with the patients' attributes, biochemical tests, and physical function, considering the achievement or non-achievement of independent walking as dependent variables, and factors that were significantly different between the 2 groups in the univariate analysis (P.05) as independent variables, after adjusting for age, sex, and body mass index. Moreover, we calculated cutoff values from the receiver operating characteristic (ROC) curves.All patients suffered from severe hepatic dysfunction (Child-Pugh class C). The mobility Functional Independence Measure score following rehabilitation was positively correlated with the psoas major muscle index within 1 month after LDLT and at the beginning of physiotherapy. The only factor associated with achieving independent walking at the end of physiotherapy (on discharge) was the psoas major muscle index within 1 month of LDLT (odds ratio = 35.03, P.05), and its cutoff value, calculated from the ROC curves curve, was 4.46.Psoas major skeletal muscle mass is a reliable index for independent walking after LDLT.

We developed a new Physical Score (PS) consisting of comprehensive physical fitness indicators and elucidated the association between the resultant PS and metabolic diseases, i.e., diabetes, hypertension, dyslipidemia, fatty liver, and metabolic syndrome (MetS), among Japanese. Analyzed were 49,850 persons (30,039 men) aged 30 to 69 y who underwent physical fitness tests. Principal component analysis was performed on the correlation matrix of the physical fitness test results (relative grip strength, single-leg balance with eyes closed, and forward bending) according to sex and age. We defined the PS as the first principal component score. A formula was developed for various age groups comprised of men and women from 30 to 69 years of age from which the PS for each age and sex was calculated. The PS for both men and women was normally distributed with a value of 0 ± 1.15-1.16. Multivariate logistic regression analysis showed that the risk of metabolic diseases increased approximately 1.1-1.6 times per each 1-point reduction in the PS. The association between PS and MetS was particularly strong in that a 1-point reduction in the PS increased the risk of MetS by 1.54 times (95% confidence interval 1.46 to 1.62) in men and by 1.21 times (1.15 to 1.28) in women. The association between a lower PS and disease risk was stronger in younger men for fatty liver and in older men for MetS. Conversely, in women, the association between a lower PS and disease risk was stronger in older women for fatty liver and in younger women for MetS. For diabetes, hypertension, and dyslipidemia, the change in the impact of PS reductions across age groups was small. The PS is a useful and simple non-invasive tool for screening Japanese people for metabolic diseases.

Background and objectives To clarify whether the presence or absence of fast walking and habitual physical activity are independently associated with the incidence of functional disability. Methods This historical cohort study was comprised of 9,652 (4,412 men, mean age 65 years) individuals aged 39–98 years without functional disability at baseline. Functional disability was determined based on the Japanese long-term care insurance system, which specified requirements for assistance in the activities of daily living. The impact of fast walking and habitual physical activity on the incidence of functional disability was analysed by Cox proportional hazards models. Results The follow-up period was a median of 3.7 years during which 165 patients were newly certified as having functional disability. In the multivariate analysis, baseline age in 5-year increments (hazard ratio 2.42 [95% confidence interval 2.18–2.69]), no habitual physical activity (1.56 [1.07–2.27]), and not fast walking (1.89 [1.32–2.69]) significantly increased the risk of functional disability after adjustment for covariates. The stratified analysis showed that compared with physical activity (+), the impact of physical activity (−) on the incidence of functional disability was observed in those aged ≥75 years regardless of fast walking (+). Fast walking (−) significantly increased the risk of disability compared with fast walking (+) in those aged Conclusion In Japanese, slow walking speed and lack of a physical activity habit were shown to be independent risk factors for incident functional disability, with their impact differing according to age.

Elevated serum uric acid reportedly increases the risk of development and progression of diabetic retinopathy with conflicting results. However, whether it also increases the incidence of severe vision-threatening diabetic eye diseases has been scarcely investigated. Also unknown is whether there are sex differences in the incidence of advanced retinopathies. To clarify this, we utilized ICD-and medical treatment codes from a nationwide claims database that finally included 13,721 type 2 diabetes patients (mean age 50 y, HbA1c 7.0%, mean follow-up period 5.8 y, 10,962 men) . During the study period, 388 patients developed vision-threatening treatment-required diabetic eye diseases (4.9/1000 person-years) . Multivariate Cox analysis demonstrated that a serum uric acid ≥7.1 mg/dl was significantly positively associated in men with future occurrence of treatment-required diabetic eye diseases, but not in women. Hazard ratios for those with serum uric acid ≥7.1 mg/dl for incident treatment-required diabetic eye diseases were 1.36 (95% confidence interval, 1.01-1.85) in men and 2. (0.71-6.08) in women, compared with the reference group ( Disclosure M. Yamamoto: None. K. Fujihara: None. H. Ishiguro: None. M. Ishizawa: None. M.H. Yamada: None. T. Osawa: None. M. Kitazawa: None. M. Kaneko: None. M. Iwanaga: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. Funding The Japan Society for the Promotion of Science and the Ministry of Health, Labor and Welfare, Japan. (18K17897)

Although we showed a significant association of poor adherence to OHAs with start of dialysis, this relationship according to the estimated glomerular filtration rate (eGFR) was not clarified. Patients with eGFR Disclosure Y.Yaguchi: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. K.Fujihara: None. M.H.Yamada: None. Y.Matsubayashi: None. T.Yamada: None. M.Iwanaga: None. M.Kitazawa: None. M.Yamamoto: None. S.Kodama: None.

This study aims to examine the impact of the association between metabolic syndrome (MetS) and metabolic dysfunction-associated fatty liver disease (MAFLD) , which both have insulin resistance and are pathophysiologically similar, on the development of new-onset cardiovascular disease, with and without type 2 diabetes mellitus (T2DM) A total of 570,426 participants without a history of cardiovascular disease who were enrolled in the nationwide claims database from 2008-2016 were included in this study. Participants were classified according to the presence or absence of MetS and/or MAFLD, and the risk of developing coronary artery disease (CAD) and/or cerebrovascular disease (CVD) in each category was analyzed using a multivariate Cox proportional hazard model. The same analysis was performed with stratification by the presence or absence of T2DM. During a median follow-up of 5.2 years, 2,252 CAD and 3,128 CVD events occurred. The hazard ratio (HR) (95% CI) for CAD, compared with the group with neither MAFLD nor MetS, was 1.46 (1.32-1.62) for MAFLD only (without MetS) , 2.02 (1.51-2.70) for MetS only (without MAFLD) , and 2.33 (2.10-2. 58) for MAFLD + MetS. For CVD, The HR was 1.41 (1.28-1.55) for MAFLD only, 1.67 (1.38-2.02) for MetS only, and 1.89 (1.72-2.08) for MAFLD + MetS. These results were similar for non-T2DM participants but different for T2DM participants, with no significant increased risk for CAD in MetS only and a significant increased risk for CVD only when both MAFLD and MetS coexisted. The predictive ability for cardiovascular disease development in patients with MetS and MAFLD differed depending on the presence or absence of T2DM. These results suggest that distinguishing between the diagnosis of MetS and MAFLD, taking into account the presence or absence of T2DM, may lead to more accurate identification of patients at high risk of developing cardiovascular disease. Disclosure K. Fujihara: None. M.H. Yamada: None. M. Yamamoto: None. H. Ishiguro: None. M. Kitazawa: None. M. Iwanaga: None. S. Kodama: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. Funding The Japan Society for Promotion of Science (JSPS) KAKENHI Grant Number JP 20K19706)

Since advanced microangiopathy of diabetes severely impairs activities of daily living (ADL) and quality of life (QoL) and macroangiopathy is life-threatening regardless of severity, treatment of diabetes requires appropriate risk management to avoid all such complications. However, current studies have analyzed and reported diabetes complications separately, despite varying incident rates and impacts on ADL/QoL and severity of illness. It is difficult to determine which predictors should be prioritized when extrapolating the results of these studies to the comprehensive care of individual patients. We defined the combined severe diabetic complications as a new life-altering outcome and determined the association of established risk factors with combined severe diabetic complications. We analyzed data from a nationwide database involving 36,994 participants with diabetes mellitus without any prior life-altering complication of diabetes during 2008-19. Combined severe diabetic complications included severe diabetic eye disease, initiating dialysis, coronary artery disease (CAD) , cerebrovascular disease (CVD) , heart failure (HF) , or amputation which were determined according to ICD-codes, medication and medical procedures. During a median follow-up period of 5.0 years, the following events occurred: severe diabetic eye disease, 774; dialysis initiated, 134: CAD, 703; CVD, 535; HF, 161; and amputations, 31. Multivariate Cox regression model showed the HRs per 1SD for combined severe diabetic complications of HbA1c, SBP, current smoking, HDL-C, BMI and LDL- C were 1.54 (1.49-1.59) , 1.37 (1.31-1.42) , 1.35 (1.23-1.48) , 0.83 (0.79-0.88) , 0.85 (0.81-0.90) and 1. (1.06-1.16) , respectively. We found that HbA1c was the most strongly associated with combined severe diabetic complications among established risk factors. Also, our results implied the necessity of revisiting the value of BMI in risk management for combined severe diabetic complications. Disclosure Y.Yaguchi: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. K.Fujihara: None. M.H.Yamada: None. Y.Matsubayashi: None. T.Yamada: None. M.Iwanaga: None. M.Kitazawa: None. M.Yamamoto: None. S.Kodama: None.

Although a linear relationship between SBP and risk of coronary artery disease or cerebrovascular disease was observed regardless of GTS, this association in HF is little known. We analyzed data from a nationwide claims database from 20to 20on 589,621 individuals. A Cox proportional hazards model identified risks of HF among 5 levels of SBP according to GTS [i.e. normal glucose tolerance (NGT) , prediabetes, diabetes (DM) ]. Incidence of HF per 1,000 person-years was 0.for NGT, 0.18 for prediabetes, and 0.80 for DM. Compared with SBP Disclosure K.Fujihara: None. M.H.Yamada: None. M.Yamamoto: None. M.Oe: None. T.Osawa: None. M.Iwanaga: None. T.Yamada: None. S.Kodama: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. Funding JSPS (21K11569)

Insulin and its secretagogues are essential for some patients with type 2 diabetes (T2D) to maintain glycemic control (GC) . However, these drugs are inevitably accompanied by hypoglycemia. Avoiding severe hypoglycemia (SH) is essential considering its poor prognosis. This network meta-analysis aimed to find optimal hypoglycemic treatment regimens for T2D in terms of GC and SH. MEDLINE and EMBASE were used to identify trials comparing 2 or more treatments including insulins and/or SU/glinide and included both GC and SH in study outcomes. Treatment hierarchy was summarized as the surface under cumulative ranking probabilities (SUCRA) . There were 137 eligible trials from which 36 treatments were identified. Insulin plus (+) non-insulin drugs except for SU/glinide (others) had a higher SUCRA for changes in hemoglobin A1c (A1C) compared with only insulins (68.2±5.6% vs. 39.9±6.6%; P=0.01) although the difference in the SUCRA for SH was not significant (P=0.59) . Compared with only insulins, SU/glinide + others had a lower SUCRA for SH (42.4±5.8% vs. 58.5±3.4%, P=0.05) and comparable SUCRA for A1C change (P=1.00) . Cluster analysis indicated that premixed insulin + glucagon-like peptide-1 receptor agonist (Mix-ins+GLP1) consistently belonged to the high-efficacy group for A1C change and achievement of A1C Disclosure S.Kodama: None. K.Kato: None. K.Watanabe: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. T.Sato: None. M.H.Yamada: None. M.Yamamoto: None. Y.Matsubayashi: None. H.Ishiguro: None. M.Iwanaga: None. K.Fujihara: None. T.Yamada: None.

Breslow’s Health Practice Index (HPI) includes recommendations for a healthy lifestyle and is composed of 7 simple lifestyle factors (sleep, breakfast, snacks, body mass index (BMI) , physical activity, drinking alcohol, and smoking status) . Cardiovascular health metrics (CVHMs) defined according to the American Heart Association are composed of lifestyle factors and clinical laboratory values (smoking status, BMI, physical activity, diet, systolic blood pressure In summary, not only to follow a healthy lifestyle but to achieve laboratory treatment targets may be essential in people with diabetes. Disclosure T.Iijima: None. T.Yamada: None. S.Kodama: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. K.Fujihara: None. M.H.Yamada: None. M.Yamamoto: None. T.Osawa: None. Y.Matsubayashi: None. T.Sato: None. Y.Yaguchi: None. M.Iwanaga: None.

BackgroundThe prevalence of diabetes is rising, and diabetes develops at a younger age in East Asia. Although lower limb amputation negatively affects quality of life and increases the risk of cardiovascular events, little is known about the rates and predictors of amputation among persons with diabetes from young adults to those in the “young-old” category (50–72 y).MethodsWe analyzed data from a nationwide claims database in Japan accumulated from 2008 to 2016 involving 17,288 people with diabetes aged 18–72 y (mean age 50.2 y, HbA1c 7.2%). Amputation occurrence was determined according to information from the claims database. Cox regression model identified variables related to lower limb amputation.ResultsThe mean follow-up time was 5.3 years, during which time 16 amputations occurred (0.17/1000 person-years). Multivariate Cox regression analysis showed that age (hazard ratio [HR] 1.09 [95% confidence intervals] 1.02–1.16,p = 0.01) and HbA1c (HR 1.46 [1.17–1.81],p ConclusionsAge and HbA1c were associated with amputations among diabetic individuals, and the rates of amputation were significantly greater in those ≥60 years old and with HbA1c ≥8.0%.

Aims Little is known about the relationship between medication adherence for oral hypoglycemic agents (OHAs) and glycemic control after adjusting healthy adherer effect in large scale study. Thus, adjusting for health-related behaviors, we investigated the clinical variables associated with medication adherence and the relationship between medication adherence and glycemic control using a large claims database. Methods Analyzed were 8805 patients with diabetes whose medication records for OHA were available for at least 1 year. Medication adherence was evaluated by the proportion of days covered (PDC). Multivariate logistic regression model was used to identify clinical variables significantly associated with non-adherence. Multiple regression analysis evaluated the relationship between PDC and HbA1c after adjusting for health-related behaviors. Results Mean PDC was 80.1% and 32.8% of patients were non-adherence. Logistic analysis indicated that older age and taking concomitant medications were significantly associated with adherence while skipping breakfast (odds ratio 0.66 [95% CI 0.57–0.76]), late-night eating (0.86 [0.75–0.98]), and current smoking (0.89 [0.80–0.99]) were significantly associated with non-adherence. Conclusions Skipping breakfast, late-night eating and current smoking were significantly associated with medication adherence, suggesting that clinicians pay attention to those health-related behaviors to achieve good medication adherence.

ObjectivesIt has been hypothesised that smoking intensity may be related to occupational stress. This study aimed to investigate whether stress, including problems with superiors or co-workers, is a driver of smoking.DesignCross-sectional study.Setting and participants59 355 employees (34 865 men and 24 490 women) across multiple occupations who completed a self-reported questionnaire-based occupational stress survey between April 2016 and March 2017 in Niigata Prefecture.Main outcome measuresStress scores for the Brief Job Stress Questionnaire subscales summed up after assigning high points for high stress and converted to Z-scores based on the mean of all participants. Heavy smokers (HS) smoked ≥15 cigarettes/day and light smokers (LS) smoked ResultsThe main subscale items that were significantly associated with smoking status in both genders included ‘physical burden’, ‘irritation’ and ‘physical symptoms’. In the analysis that included smoking intensity, the stress score for ‘co-workers’ support’ was significantly lower for LS men than NS men (NS 0.091±0.98, LS −0.027±1.00, HS 0.033±0.99), and was significantly higher for HS women than NS women (NS −0.091±1.00, LS −0.080±1.05, HS 0.079±1.03). However, the stress score for ‘co-workers’ support’ was low among LS women aged ≤39 years in the manufacturing industry.ConclusionsIt was speculated that LS men and some LS women gained ‘co-workers’ support’ using smoking as a communication tool while reducing the degree of smoking. The existence of such ‘social smokers’ suggested that to promote smoking cessation, measures are essential to improve the communication between workers in addition to implementing smoking restrictions in the workplace.

This network meta-analysis aimed to assess the current efficacy of decreasing the uric acid (UA) level with drugs to reduce mortality in patients with heart failure (HF). Electronic literature searches using EMBASE and MEDLINE of studies published from 1 Jan 1950 to 26 Dec 2019 were conducted for randomized controlled trials or non-randomized cohort studies that included at least one group of patients who took UA-lowering drugs and with a study outcome of all-cause mortality. A random-effects network meta-analysis was performed within a frequentist framework. Hierarchy of treatments was expressed as the surface under the cumulative ranking curve (SUCRA) value, which is in proportion to mean rank (best is 100%). Nine studies, which included seven different types of groups, were eligible for analysis. The “untreated uricemia” group in which patients had hyperuricemia but without treatment had a significantly higher risk of mortality than the “no uricemia” group in which patients had no hyperuricemia (relative risk (RR)(95% confidence interval (CI), 1.43 (1.08–1.89)). The “start-allo” group wherein patients started to take allopurinol did not have a significantly lower risk of mortality than the “untreated uricemia” group (RR (95% CI), 0.68 (0.45–1.01)). However, in the “start-allo” group the SUCRA value was comparable to that in the “no uricemia” group (SUCRA: 65.4% for “start-allo”; 64.1% for “no uricemia”). Results suggested that allopurinol therapy was not associated with a significantly improved prognosis in terms of mortality but could potentially counteract the adverse effects associated with longstanding hyperuricemia in HF patients.

Aim To examine the association between treatment-achieved HbA1c values and incidence of both coronary artery disease (CAD) and severe eye disease with different diabetes treatments. Methods Associations of treatment-achieved HbA1c were investigated in various treatment groups [diet only; insulin; sulphonylurea (SU) alone; SU with glinides; and antihyperglycaemic agents other than glinides, SU or insulin] taken from a nationwide claims database of 14,633 Japanese diabetes patients. Cox’s regression analysis examined risks over a 5.1-year follow-up. Results A significant linear trend was associated with HbA1c levels and CAD events in the diet-only group, and CAD risks were significantly higher in insulin and SU groups with HbA1c ≤ 7.0% and > 8.0% than in the diet-only group with HbA1c ≤ 7.0%. In contrast to CAD, a linear association was observed regardless of treatment modality between achieved HbA1c levels and risk of severe diabetic eye disease, but with no significant difference in eye disease risk between groups with HbA1c ≤ 7.0% and 7.1–8.0% in those treated with either SU alone, SU with glinides, or insulin. Conclusion These findings suggest that the relationship between treatment-achieved HbA1c and incidence of both CAD and severe diabetic eye disease differed according to treatment, based on a large-scale real-life database. More research is now needed to confirm these findings and to further investigate the underlying mechanisms.

Recently, an increasing number of cohort studies have suggested using machine learning (ML) to predict type 2 diabetes mellitus. However, its predictive ability remains inconclusive. This meta-analysis evaluated the current ability of ML algorithms for predicting incident type 2 diabetes mellitus.We systematically searched longitudinal studies published from 1 January 1950 to 17 May 2020 using MEDLINE and EMBASE. Included studies had to compare ML's classification with the actual incidence of type 2 diabetes mellitus, and present data on the number of true positives, false positives, true negatives and false negatives. The dataset for these four values was pooled with a hierarchical summary receiver operating characteristic and a bivariate random effects model.There were 12 eligible studies. The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 0.81 (95% confidence interval [CI] 0.67-0.90), 0.82 [95% CI 0.74-0.88], 4.55 [95% CI 3.07-6.75] and 0.23 [95% CI 0.13-0.42], respectively. The area under the summarized receiver operating characteristic curve was 0.88 (95% CI 0.85-0.91).Current ML algorithms have sufficient ability to help clinicians determine whether individuals will develop type 2 diabetes mellitus in the future. However, persons should be cautious before changing their attitude toward future diabetes risk after learning the result of the diabetes prediction test using ML algorithms.

It is unclear whether genetic interactions are involved in the association between vegetable intake and reduced body mass index (BMI) or obesity. We conducted a comprehensive search for single nucleotide polymorphisms (SNPs) which are associated with the interaction between vegetable intake frequency and BMI or obesity. We performed a genome-wide association analysis to evaluate the genetic interactions between self-reported intake of vegetables such as carrot, broccoli, spinach, other green vegetables (green pepper and green beans), pumpkin, and cabbage with BMI and obesity, which is defined as a BMI ≥ 25.0 kg/m2 in the Japanese population (n = 12,225). The mean BMI and prevalence of obesity was 23.9 ± 3.4 kg/m2 and 32.3% in men and 22.1 ± 3.8 kg/m2 and 17.3% in in women, respectively. A significant interaction was observed between rs4445711 and frequency of carrot intake on BMI (p = 4.5 × 10−8). This interaction was slightly attenuated after adjustment for age, sex, alcohol intake, smoking, physical activity and the frequency of total vegetable intake (p = 2.1 × 10−7). A significant interaction was also observed between rs4445711 and frequency of carrot intake on obesity (p = 2.5 × 10−8). No significant interactions that were the same as the interaction between frequency of carrot intake and rs4445711 were observed between the intake frequency of broccoli, spinach, other green vegetables, pumpkin or cabbage and BMI or obesity. The frequency of carrot consumption is implicated in reducing BMI by the intermediary of rs4445711. This novel genetic association may provide new clues to clarify the association between vegetable intake and BMI or obesity.

Our purpose in the research was to clarify the impact of medication adherence to oral hypoglycemic agents during a 1-year period and subsequent glycemic control on the risk of micro- and macrovascular diseases.Examined was a nationwide claims database on 13,256 individuals with diabetic eye disease without requiring prior treatment, 7,862 without prior initiation of dialysis, 15,556 without prior coronary artery disease, 16,243 without prior cerebrovascular disease, and 19,386 without prior heart failure from 2008 to 2016 in Japan. Medication adherence was evaluated by the proportion of days covered. Patients were considered to have poor adherence if the proportion of days covered was80%. Multivariate Cox regression model identified risks of micro- and macrovascular diseases.In each group, mean age was 53 to 54 years, HbA1c was 7.1% to 7.2%, and median follow-up period was 4.6 to 5.1 years, and the percentage of poor adherence was approximately 30%. During the study period, 532 treatment-requiring diabetic eye disease, 75 dialysis, 389 coronary artery disease, 316 cerebrovascular disease, and 144 heart failure events occurred. Multivariate Cox regression model revealed that the hazard ratio (95% confidence interval) of dialysis in the poor adherence group was 2.04 (1.27-3.30) compared with the good adherence group. The hazard ratios in the poor adherence/poor glycemic control group were 3.34 (2.63-4.24) for treatment-requiring diabetic eye disease, 4.23 (2.17-8.26) for dialysis, 1.69 (1.23-2.31) for coronary artery disease, and 2.08 (1.25-3.48) for heart failure compared with the good adherence/good glycemic control group.Poor medication adherence was an independent risk factor for the initiation of dialysis, suggesting that clinicians must pay close attention to these patients.

We investigated the impact of medication adherence for a one-year period and subsequent glycemic control and their combinations on the risk of micro/macrovascular diseases among Japanese using nationwide claims data. Analyzed were 19,565 patients with diabetes whose medication records for oral hypoglycemic agents (OHAs) were available for at least 1 year without prior treatment-requiring diabetic eye disease (TRDED), initiation of dialysis (dialysis), coronary artery disease (CAD), or cerebrovascular disease (CVD), respectively (mean age 53y, HbA1c 7.2%). Medication adherence was evaluated by the proportion of days covered (PDC), and PDC Disclosure Y. Yaguchi: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. K. Fujihara: None. M. H. Yamada: None. Y. Matsubayashi: None. T. Yamada: None. M. Iwanaga: None. M. Kitazawa: None. M. Yamamoto: None. S. Kodama: None.

Heavy total alcohol consumption was reported to increase the risk of development and progression of diabetic retinopathy. However, differing from total alcohol consumption, whether the quantity of alcohol intake per occasion had harmful or beneficial effects related to severe eye diseases caused by diabetes remains unknown. To clarify this, we utilized ICD-10 and medical treatment codes from a nationwide claims database that finally included 21,392 men with type 2 diabetes (mean age 53 y, HbA1c 7.0%, mean follow-up period 4.3 y). During the study period, 425 patients developed vision-threatening treatment-required diabetic eye diseases (TRDED) (4.6/1000 person-years). Multivariate Cox analysis demonstrated that a large quantity of alcohol per occasion defined as ≥3 drinks per occasion was positively associated with future occurrence of TRDED. One drink was defined as a standard Japanese drink with a volume equivalent to 23 g ethanol. Hazard ratio in patients drinking large amounts of alcohol per occasion for incident TRDED was 4.49 (95% confidence interval, 1.98-10.19) compared with the reference group (≤1 drink per occasion) after adjusting for covariates including total alcohol consumption. This finding demonstrated that a large quantity of alcohol per occasion had a significant association with future vision-threatening retinopathy in men with type 2 diabetes. The mechanism of this finding with regard to severe retinopathy awaits further research. Disclosure M. Yamamoto: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. K. Fujihara: None. Y. Yaguchi: None. T. Osawa: None. M. Kaneko: None. M. Kitazawa: None. T. Sato: None. M. H. Yamada: None. Y. Matsubayashi: None.

Background Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity. Objective To assess the efficacy and safety of benralizumab in patients with ECRS. Methods This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12. Results Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, −0.5 ± 0.8; benralizumab single, −0.3 ± 0.8; benralizumab q4w, −0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted. Conclusion Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.

Purpose To evaluate the accuracy of various claims-based definitions of diabetes-related complications (coronary artery disease [CAD], heart failure, cerebrovascular disease and dialysis). Methods We evaluated data on 1379 inpatients who received care at the Niigata University Medical & Dental Hospital in September 2018. Manual electronic medical chart reviews were conducted for all patients with regard to diabetes-related complications and were used as the gold standard. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each claims-based definition associated with diabetes-related complications based on Diagnosis Procedure Combination (DPC), International Classification of Diseases, Tenth Revision (ICD-10) codes, procedure codes and medication codes were calculated. Results DPC-based definitions had higher sensitivity, specificity, and PPV than ICD-10 code definitions for CAD and cerebrovascular disease, with sensitivity of 0.963-1.000 and 0.905-0.952, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. Sensitivity, specificity, and PPV were high using procedure codes for CAD and dialysis, with sensitivity of 0.963 and 1.000, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. DPC and/or ICD-10 codes + medication were better for heart failure than the ICD-10 code definition, with sensitivity of 0.933, specificity of 1.000, and PPV of 1.000. The PPVs were lower than 60% for all diabetes-related complications using ICD-10 codes only. Conclusion The DPC-based definitions for CAD and cerebrovascular disease, procedure codes for CAD and dialysis, and DPC or ICD-10 codes with medication codes for heart failure could accurately identify these diabetes-related complications from claims databases.

Background Machine learning (ML) algorithms have been widely introduced to diabetes research including those for the identification of hypoglycemia. Objective The objective of this meta-analysis is to assess the current ability of ML algorithms to detect hypoglycemia (ie, alert to hypoglycemia coinciding with its symptoms) or predict hypoglycemia (ie, alert to hypoglycemia before its symptoms have occurred). Methods Electronic literature searches (from January 1, 1950, to September 14, 2020) were conducted using the Dialog platform that covers 96 databases of peer-reviewed literature. Included studies had to train the ML algorithm in order to build a model to detect or predict hypoglycemia and test its performance. The set of 2 × 2 data (ie, number of true positives, false positives, true negatives, and false negatives) was pooled with a hierarchical summary receiver operating characteristic model. Results A total of 33 studies (14 studies for detecting hypoglycemia and 19 studies for predicting hypoglycemia) were eligible. For detection of hypoglycemia, pooled estimates (95% CI) of sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 0.79 (0.75-0.83), 0.80 (0.64-0.91), 8.05 (4.79-13.51), and 0.18 (0.12-0.27), respectively. For prediction of hypoglycemia, pooled estimates (95% CI) were 0.80 (0.72-0.86) for sensitivity, 0.92 (0.87-0.96) for specificity, 10.42 (5.82-18.65) for PLR, and 0.22 (0.15-0.31) for NLR. Conclusions Current ML algorithms have insufficient ability to detect ongoing hypoglycemia and considerate ability to predict impeding hypoglycemia in patients with diabetes mellitus using hypoglycemic drugs with regard to diagnostic tests in accordance with the Users’ Guide to Medical Literature (PLR should be ≥5 and NLR should be ≤0.2 for moderate reliability). However, it should be emphasized that the clinical applicability of these ML algorithms should be evaluated according to patients’ risk profiles such as for hypoglycemia and its associated complications (eg, arrhythmia, neuroglycopenia) as well as the average ability of the ML algorithms. Continued research is required to develop more accurate ML algorithms than those that currently exist and to enhance the feasibility of applying ML in clinical settings. Trial Registration PROSPERO International Prospective Register of Systematic Reviews CRD42020163682; http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42020163682